Journal Article

Antiherpes Virus–Specific Treatment and Cognition in Schizophrenia: A Test-of-Concept Randomized Double-Blind Placebo-Controlled Trial

Konasale M. Prasad, Shaun M. Eack, Matcheri S. Keshavan, Robert H. Yolken, Satish Iyengar and Vishwajit L. Nimgaonkar

in Schizophrenia Bulletin

Published on behalf of Maryland Psychiatric Research Center

Volume 39, issue 4, pages 857-866
Published in print July 2013 | ISSN: 0586-7614
Published online March 2012 | e-ISSN: 1745-1701 | DOI: https://dx.doi.org/10.1093/schbul/sbs040
Antiherpes Virus–Specific Treatment and Cognition in Schizophrenia: A Test-of-Concept Randomized Double-Blind Placebo-Controlled Trial

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Objective

To test our hypothesis that valacyclovir, an antiherpes virus–specific medication, added to antipsychotics (APs) would improve cognitive performance and psychopathology among schizophrenia subjects exposed to neurotropic herpes simplex virus, type 1 (HSV1).

Methods

Using a double-blind placebo-controlled design, we randomized 24 HSV1-seropositive schizophrenia subjects to receive either valacyclovir (n = 12) or placebo (n = 12) for 18 weeks in addition to stable doses of APs. Valacyclovir dose was stabilized at 1.5 g twice daily orally. At each visit, subjects were evaluated for severity of psychopathology and side effects using standardized scales and a study-specific semistructured checklist. A computerized neurocognitive battery validated on both schizophrenia and healthy subjects was administered at baseline and follow-up. Intent-to-treat analysis, using linear regression models that included all randomized subjects, were used to examine differential changes in cognition and psychopathology scores over 18 weeks between valacyclovir and placebo, accounting for placebo response.

Results

Valacyclovir group improved in verbal memory, working memory, and visual object learning compared with placebo group. The effect sizes (Cohen’s d) were 0.79 for working memory, 1.14 for immediate verbal memory, and 0.97 for the visual object learning. Psychotic symptom severity did not improve.

Conclusions

Supplemental valacyclovir may alleviate impairments in cognitive domains that are often observed in schizophrenia but not psychotic symptoms in those exposed to HSV1. If replicated, this approach could provide a novel strategy to treat cognitive impairments in a subgroup of schizophrenia subjects who can be reliably identified using a blood test.

Keywords: psychosis; cognitive impairments; therapeutics; valacyclovir; herpes simplex virus; neurotropic viruses

Journal Article.  5734 words.  Illustrated.

Subjects: Child and Adolescent Psychiatry

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